The purpose of this investigation is to examine host-treponeme interactions and characterize the roles of both humoral and cell-mediated immunity during the course of experimental Treponema pallidum infection in inbred strains of guinea pigs. Guinea pigs infected intradermally with T. pallidum regularly develop treponeme-containing skin lesions during the early stages of the disease followed by the rapid dissemination of virulent organisms to the draining lymph nodes. We will determine during primary syphilitic infection, when antibodies are produced which specifically recognize unique treponemal proteins. These kinetic studies will be done by separating polypeptides of T. pallidum electrophoretically followed by reacting them with serum immunoglobulins from infected guinea pigs. Based on these Western blotting techniques, molecular characterization of the polypeptide antigens of T. pallidum reactive with syphilitic serum will be achieved. Samples of IgG recognizing unique treponemal proteins will be fractionated into subclasses (IgG1 & IgG2) and will be tested for anti-treponemal activity as measured by in vitro-in vivo neutralization tests. Guinea pigs develop maximum resistance to cutaneous challenge infection 6-8 months after the primary "immunizing" infection. Lymphoid cells from such immune animals have the capacity to transfer protection to recipients subsequently challenged with T. pallidum. Experiments will be performed whereby the course of T. pallidum infection will be studied in guinea pigs made selectively immunodeficient for either thymus-dependent immunity or the B-cell component of the immune response followed by the infusion of syphilis immune lymphocytes. With this adoptive transfer system, it should be possible to determine the manner in which T lymphocytes interact with other cell types (e.g. B cells & macrophages) in the generation and expression of an effective anti-treponemal immune response. The final set of experiments will examine the ability of T. pallidum-induced suppressor mechanisms to interfere with intrinsic lymphocyte responses in vitro as well as with the generation and expression of protective immunity in vivo.